ISSN:0009-7330    

出版商:OVID    

年代:2001

数据来源: OVID

ISSN:0009-7330    

出版商:OVID    

年代:2001

数据来源: OVID

ISSN:0009-7330    

出版商:OVID    

年代:2001

数据来源: OVID

ISSN:0009-7330    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Secretory phospholipase A2(PLA2) can be proatherogenic both in the circulation and in the arterial wall. In blood plasma, PLA2can modify the circulating lipoproteins and so induce formation of small dense LDL particles, which are associated with increased risk for cardiovascular disease. In the arterial wall, PLA2can hydrolyze lipoproteins. The PLA2-modified lipoproteins bind tightly to extracellular proteoglycans, which may lead to their enhanced retention in the arterial wall. The modified lipoproteins may also aggregate and fuse, which can lead to accumulation of their lipids within the extracellular matrix. The PLA2-modified particles are more susceptible to further modifications by other enzymes and agents and can be taken up by macrophages, leading to accumulation of intracellular lipids. In addition, lysophospholipids and free fatty acids, the hydrolysis products of PLA2, promote atherogenesis. Thus, these lipid mediators can be carried, either by the PLA2-modified lipoproteins themselves or by albumin, into the arterial cells, which then undergo functional alterations. This may, in turn, lead to specific changes in the extracellular matrix, which increase the retention and accumulation of lipoproteins within the matrix. In the present article, we discuss the possible actions of PLA2enzymes, especially PLA2-IIA, in the arterial wall during atherogenesis.

ISSN:0009-7330    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

The study of atherosclerotic disease during its natural history and after therapeutic intervention will enhance our understanding of disease progression and regression and aid in selecting appropriate treatments. Several invasive and noninvasive imaging techniques are available to assess atherosclerotic vessels. Most of the standard techniques identify luminal diameter, stenosis, wall thickness, and plaque volume; however, none can characterize plaque composition and therefore identify the high-risk plaques. We will present the different imaging modalities that have been used for the direct assessment of the carotid, aortic, and coronary atherosclerotic plaques. We will review in detail the use of high-resolution, multicontrast magnetic resonance for the noninvasive imaging of vulnerable plaques and the characterization of plaques in terms of their various components (ie, lipid, fibrous, calcium, or thrombus).

ISSN:0009-7330    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

The pathogenesis of salt-sensitive hypertension remains poorly defined, but a role for nitric oxide (NO) has been suggested. The Dahl/Rapp salt-sensitive rat possesses a defect in NO synthesis that is overcome by supplementation with l-arginine, which increases NO and cGMP production and prevents salt-sensitive hypertension. An S714P mutation of inducible NO synthase (NOS2) was subsequently identified. The current report examined the functional significance of an S714P mutation in NOS2. COS-7 cells were transiently transfected with cDNA of wild-type NOS2 and S714P and S714A mutants of NOS2, and enzyme function was determined. Whereas steady-state mRNA levels did not differ, immunoblot analysis demonstrated decreased levels of NOS2 protein. Metabolic labeling experiments confirmed a reduced half-life of the S714P mutation. Nitrite production, which was dependent on the concentration of l-arginine in the medium, was diminished in cells transfected with the S714P mutant, compared with the wild type and the S714A mutant. These data provide a biochemical explanation of the physiological abnormalities of NOS2 in the Dahl/Rapp salt-sensitive rat and suggest that a posttranslational mechanism involving the proteasome may be responsible for the diminished NO production observed in response to increased dietary salt intake in these animals.

ISSN:0009-7330    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Inhibition of proliferative neointima formed by vascular smooth muscle cells is a potential target in preventing angioplasty-induced restenosis. We have created a potent antiproliferative by fusing the active regions of the p27 and p16 cell cycle inhibitors. Intravascular delivery of a replication-deficient adenoviral vector (AV) encoding this p27-p16 fusion protein, named W9, inhibited balloon injury–induced neointimal hyperplasia in rabbit carotid arteries. In a therapeutically more relevant model, AV-W9 was delivered to balloon-injured porcine coronary arteries in vivo using an infusion catheter. Of the three coronary arteries, two were injured with a 15-mm balloon catheter and either were left untreated or were treated with 1012viral particles of either AV-W9 or a control null virus. AV-W9 treatment significantly inhibited neointimal hyperplasia in this porcine arterial balloon injury model compared with untreated or control virus–treated vessels. The average intimal area of the AV-W9–treated group 10 days after balloon injury and treatment was 0.42±0.36 mm2, whereas the AV-null group demonstrated an intimal area of 0.70±0.52 mm2. At day 10 the average intimal thickness of the AV-W9–treated vessels was 9.1 &mgr;m (n=5, ×20 magnification) compared with 21.2 &mgr;m (n=5, ×20 magnification) in control virus–treated vessels. This trend was also observed at 28 days after balloon injury and gene transfer during which AV-W9–treated vessels demonstrated an average intimal thickness of 4.7 &mgr;m (n=8, ×20 magnification) compared with 13.3 &mgr;m (n=3, ×20 magnification) in control virus–treated vessels and 7.3 &mgr;m (n=5, ×20 magnification) in the sham-treated vessels. The AV-W9 treatment was safe and well tolerated. These data suggest that AV-W9 gene therapy may be useful in preventing angioplasty–induced intimal hyperplasia in the coronary artery.

ISSN:0009-7330    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Studies have characterized conduction velocity in the right and left bundle branches (RBB, LBB) of normal and genetically engineered mice. However, no information is available on the action potential characteristics of the specialized conduction system (SCS). We have used microelectrode techniques to characterize action potential properties of the murine SCS, as well as epicardial and endocardial muscle preparations for comparison. In the RBB, action potential duration at 50%, 70%, and 90% repolarization (APD50,70,90) was 6±0.7, 35±6, and 90±7 ms, respectively. Maximum upstroke velocity (dV/dtmax) was 153±14 V/s, and conduction velocity averaged 0.85±0.2 m/s. APD90was longer in the Purkinje network of fibers (web) than in the RBB (P<0.01). Web APD50was longer in the left than in the right ventricle (P<0.05). Yet, web APD90was longer in the right than in the left ventricle (P<0.001). APD50,70was significantly longer in the endocardial than in the epicardial (P<0.001;P<0.003). APD90in the epicardial and endocardial was shorter than in the RBB (≈36 ms versus ≈100 ms). Spontaneous electrical oscillations in phase 2 of the SCS occasionally resulted in early afterdepolarizations. These results demonstrate that APDs in the murine SCS are significantly (≈2-fold) longer than in the myocardium and implicate the role of the murine SCS in arrhythmias. The differences should have important implications in the use of the mouse heart to study excitation, propagation, and arrhythmias.

ISSN:0009-7330    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Many members of the two-pore-domain potassium (K+) channel family have been detected in the mammalian heart but the endogenous correlates of these channels still have to be identified. We investigated whetherIKAA, a background K+current activated by negative pressure (stretch) and by arachidonic acid (AA) and sensitive to intracellular acidification, could be the native correlate of TREK-1 in adult rat atrial cells. Using the inside-out configuration of the patch-clamp technique, we found thatIKAA, like TREK-1, was outwardly rectifying in physiological K+conditions, with a conductance of 41 pS at +50 mV. Like TREK-1,IKAAwas reversibly activated by clinical concentrations of volatile anesthetics (in mmol/L, chloroform 0.18, halothane 0.11, and isoflurane 0.69). In cell-attached experiments,IKAAwas inhibited by chlorophenylthio-cAMP (500 &mgr;mol/L) and also by stimulation of &bgr;-adrenergic receptors with isoproterenol (1 &mgr;mol/L). In addition, TREK-1 mRNAs were detected in all cardiac tissues, and the TREK-1 protein was immunolocalized in isolated atrial myocytes. Such a background potassium channel might contribute to the positive inotropic effects produced by &bgr;-adrenergic stimulation of the heart. It might also be involved in the regulation of the atrial natriuretic peptide secretion.

ISSN:0009-7330    

出版商:OVID    

年代:2001

数据来源: OVID